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Photothermal Nanoparticles Immune Engineer Tumor-specific T cells for Adoptive Cell Therapy

Award Number: R01CA290045
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/03/2024
PERIOD OF PERFORMANCE END DATE: 03/31/2029

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Photothermal Nanoparticles Immune Engineer Tumor-specific T cells for Adoptive Cell Therapy - PROJECT SUMMARY This goal of this proposal is to investigate a novel photothermal nanoparticle-based approach for generating tumor-specific T cells as an adoptive T cell therapy (ATCT) for glioblastoma (GBM). Despite being the most commonly diagnosed brain tumor, the prognosis for GBM patients is dismal, with a relative five-year survival rate of 7.5%. Hence, there is an urgent need for novel therapies for this patient population. In response, we are synthesizing novel Prussian blue nanoparticle-based formulations that will be used to administer photothermal therapy (PBNP-PTT) and generate a personalized ATCT for GBM. Our approach involves treating GBM tumor cells resected during surgery with PBNP-PTT ex vivo, and co-culturing them with dendritic cells (DCs) and T cells expanded from PBMCs sourced from the patient or a matched donor, to expand GBM-specific T cells for subsequent ATCT. We envision our therapy to be administered to patients after standard-of-care regimens of surgery, chemotherapy, and radiation therapy, when GBM patients are in a minimally residual disease state, with the goal of maximizing the impact of the T cell therapy thus improving survival outcomes. In a recently published study with GBM tumor cell lines, we demonstrated that PBNP-PTT generated more potent tumor-specific T cells in terms of specificity and cytolytic function, when compared to T cells generated by freeze-thaw lysis of the GBM tumor cells or by heating of the tumor cells on a heat block at equivalent thermal doses. In vivo, our immune engineered T cells eliminated orthotopically implanted U87 xenograft tumors and significantly improved survival compared to tumor-bearing animals treated with lysate-derived, antigen (PRAME)-specific, or PHA-expanded T cells, and control treatments. Operationally, our approach represents a more seamless workflow than other personalized approaches. It involves a straightforward, single administration of PBNP-PTT to the GBM cells isolated after surgery for 10 minutes using PBNPs pre-synthesized with GLP techniques and a portable laser, followed by well-established DC and T cell expansion protocols. Building on these promising findings, we now propose to synthesize multiple PBNP-PTT nanoformulations to generate and expand tumor-specific T cells and conduct studies testing their efficacy in vitro, in vivo, and ex vivo, as well as mechanistic studies. We hypothesize that PBNP-PTT of GBM tumor cells using our PBNP nanoformulations significantly enhances antigen release and capture by the PBNPs, their processing and presentation by DCs allowing more robust activation of a diverse T cell population, which subsequently differentiates into cytotoxic effector and long-lasting memory phenotypes, the ideal ATCT product for safe and effective treatment of GBM. Success in this project will demonstrate the use of PBNP-PTT nanoformulations to generate a transformative, new class of ATCT for GBM.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $354,254 )
2026	2026	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Cancer Detection and Diagnosis Research	004	4	7/6/2026	NON-COMPETING CONTINUATION	$591,169
2026	2025	GEORGE WASHINGTON UNIVERSITY (THE)	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Cancer Detection and Diagnosis Research	003	2	2/13/2026	NON-COMPETING CONTINUATION	$0
2026	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Cancer Detection and Diagnosis Research	002	3	1/23/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$236,915
2026	2025	GEORGE WASHINGTON UNIVERSITY (THE)	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Cancer Detection and Diagnosis Research	000	2	1/23/2026	NON-COMPETING CONTINUATION	-$236,915
2026	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Cancer Detection and Diagnosis Research	001	3	1/23/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$236,915
														Subtotal = $354,254

Issue Date FY: 2025 ( Subtotal = $605,957 )
2025	2025	GEORGE WASHINGTON UNIVERSITY (THE)	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Cancer Detection and Diagnosis Research	001	2	5/22/2025	NON-COMPETING CONTINUATION	$60,596
2025	2025	GEORGE WASHINGTON UNIVERSITY (THE)	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Cancer Detection and Diagnosis Research	000	2	2/17/2025	NON-COMPETING CONTINUATION	$545,361
														Subtotal = $605,957

Issue Date FY: 2024 ( Subtotal = $598,805 )
2024	2024	GEORGE WASHINGTON UNIVERSITY (THE)	1918 F ST NW	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Cancer Detection and Diagnosis Research	000	1	4/3/2024	NEW	$598,805
														Subtotal = $598,805

Grand Total All Awards = $1,559,016

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Photothermal Nanoparticles Immune Engineer Tumor-specific T cells for Adoptive Cell Therapy

Award Number: R01CA290045

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/03/2024

PERIOD OF PERFORMANCE END DATE: 03/31/2029

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